The objective of this proposal is to assess by in vitro techniques the multiplicity of human B cell subsets that arise in the circulation following booster immunization and to define the roles of T cell populations in the regulation of antibody production by these B cell subsets. By employing in vivo booster immunization in combination with the in vitro culture of antibody producing cells, we have shown that at least four distinct subpopulations of human B cells exist. These subpopulations can be distinguished from one another by: (1) the isotype of antibody produced; (2) the temporal appearance of the cells in the circulation after booster immunization; (3) the requirement for in vitro mitogen stimulation for production of antibody; and, (4) the membrane receptors on the surface of the antibody producing cells. Future work will be aimed at determining the relationship of these cells to one another and their respective roles in in vivo humoral immunity.